Perioperative Short‐Term Glucocorticoids Do Not Increase Incidence of Complications after Total Joint Arthroplasty in Patients with Rheumatoid Arthritis

Objectives The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to investigate whether similar benefits can be observed in patients with rheumatoid arthritis undergoing total joint arthroplasty. Specifically, we aim to explore the impact of perioperative glucocorticoid use on postoperative complications, opioid consumption, incidence of hypotension, hyperglycemia, 30‐day mortality, and 90‐day re‐admission in this patient population. Methods Approval for the study protocol was obtained from the Medical Research Ethics Committee at Sichuan University, aligning with the principles outlined in the Declaration of Helsinki. We retrospectively analyzed a consecutive series of patients with rheumatoid arthritis who underwent total joint arthroplasty at our medical center between November 2009 and April 2021 and who were not on chronic glucocorticoid therapy before surgery. Those who received glucocorticoids at any time during hospitalization were compared to those who did not in terms of acute complications within 90 days after surgery as well as postoperative rescue opioid consumption, hypotension, and hyperglycemia during hospitalization. The two groups were also compared in terms of overall duration of hospitalization, all‐cause mortality within 30 days, and readmission for any reason within 90 days. Continuous data were assessed for significance using the independent‐samples t test. Categorical data were assessed using the Pearson chi‐squared test. Results Of the 849 patients included in the analysis, 598 administered perioperative glucocorticoids and 251 did not. Prior to surgery, the two groups did not differ significantly in any clinicodemographic variable that we examined. The incidence of acute postoperative complications (2.3% vs. 4.0%, p = 0.187) and acute postoperative infection (2.0% vs. 2.8%, p = 0.482) was comparable between those who received perioperative glucocorticoids and those who did not, but the former group exhibited a significantly lower incidence of rescue opioid use (17.9% vs. 44.6%, p < 0.001) as well as significantly lower total rescue opioid consumption (4.7 ± 2.1 mg vs. 8.9 ± 4.6 mg, p < 0.001). However, the two groups showed similar incidences of postoperative hypotension, hyperglycemia, 30‐day mortality, and 90‐day re‐admission. Conclusion Perioperative glucocorticoids may reduce the need for rescue opioids after total joint arthroplasty of rheumatoid arthritis patients, without increasing the incidence of acute complications, hypotension or hyperglycemia.


Introduction
T otal joint arthroplasty represents a highly efficacious intervention for end-stage hip or knee disease, and perioperative corticosteroids, as part of contemporary multimodal treatment regimens, are often administered in order to relieve postoperative pain, reduce the risk of postoperative complications, and enhance recovery. 1Numerous randomized controlled trials 2,3 and meta-analyses [4][5][6][7] have consistently demonstrated that perioperative glucocorticoids can significantly reduce postoperative pain, opioid use, nausea, and vomiting without increasing risk of postoperative complications.However, most of these studies have focused on patients with osteoarthritis of hip or knee other than rheumatoid arthritis.As a result, the safety and efficacy of perioperative glucocorticoids remain controversial for patients with rheumatoid arthritis undergoing total joint arthroplasty.
0][11] Furthermore, there is a lack of studies on the safety and efficacy of perioperative glucocorticoids for patients with rheumatoid arthritis who were not previously on chronic glucocorticoid therapy before arthroplasty.
Therefore, this study aims to compare patients who received glucocorticoids preoperatively in our center with those who did not in terms of (i) incidence of postoperative complications; (ii) risk and dose of rescue opioids needed; and (iii) incidence of hyperglycemia and hypotension.

Patients
With approval from the Ethics Committee for Biomedical Research at our hospital (approval 2023-2005), we retrospectively analyzed a consecutive series of patients who (i) were diagnosed with rheumatoid arthritis based on the criteria of the American College of Rheumatology and European League Against Rheumatism 12 ; (ii) were at least 18 but no older than 80 years old; (iii) were not on chronic glucocorticoid therapy before admission; (iv) underwent primary, unilateral, total arthroplasty of the hip or knee at our hospital between November 2009 and April 2021.Patients were excluded if they (i) were lost to follow-up within 90 days after surgery; (ii) required specialized joint prostheses due to having severe preoperative bone defects.The Ethics Committee waived the requirement for informed consent because, at the time of treatment, patients or their legal guardians consented to the analysis and publication of anonymized medical data for research purposes.

Interventions and Follow-Up
All arthroplasties in this study were conducted using standard procedures under the same analgesic protocol.All patients received antibiotics during the perioperative period to prevent infection.All patients were treated with the same perioperative strategies, including tranexamic acid, pain management, thrombosis prevention, and functional rehabilitation.Selective COX-2 inhibitors have been used for pain relief.For thrombosis prophylaxis, we administered low-molecular-weight heparin after surgery until discharge.Subsequently, apixaban was continued for 2 weeks.Primary total joint arthroplasty was performed by five experienced joint surgeons using a standardized surgical approach to ensure similar surgical trauma among all patients.Nurses regularly assessed postoperative pain severity using a visual rating scale from 0 to 10. Patients indicating a score of 4 were provided with oral oxycodone, while those indicating a score of 6 or higher received intramuscular morphine until their pain rating fell below 4. Blood glucose and blood pressure levels were monitored daily during hospitalization.Patients with poorly controlled blood pressure and/or blood glucose at discharge were advised to selfmonitor regularly.
The outpatient clinic visits were scheduled for all patients at 1, 3, 6, and 12 months post-discharge, followed by annual check-ups.During each follow-up appointment, comprehensive physical examinations and X-ray assessments were conducted to detect any potential postoperative complications.

Data Collection and Outcomes
The data collected upon admission encompassed a range of clinicodemographic characteristics, including diseasemodifying anti-rheumatic drugs, Charlson comorbidity index, diabetes status, and type of anesthesia employed.Intraoperative blood loss and blood transfusion were quantified based on the anesthesia record sheet.Dosages of all glucocorticoids administered during hospitalization were standardized to dexamethasone equivalents.Patients who received any glucocorticoids during hospitalization were compared to those who received none in terms of the primary outcome, which was defined as acute complications occurring within 90 days after surgery.These complications encompassed myocardial infarction, deep vein thrombosis, pulmonary embolism, pulmonary infection, sepsis, prosthetic joint infection, superficial surgical site infection, dislocation and periprosthetic fracture.The two groups were compared in terms of the following postoperative secondary outcomes until discharge: cumulative postoperative opioid dose; incidence of hyperglycemia, defined as blood glucose ≥180 mg/ld.; and incidence of postoperative hypotension.The two groups were also compared in terms of overall duration of hospitalization, all-cause mortality within 30 days, and readmission for any reason within 90 days.

Statistical Analysis
Continuous data were reported as mean AE standard deviation (SD), or median (interquartile range), and intergroup differences were assessed for significance using the independent-samples t test.Categorical data were reported as n (%), and intergroup differences were assessed using the Pearson chi-squared test.All statistical analyses were performed using SPSS 26.0 (IBM, Armonk, NY, USA), and results associated with P < 0.05 were considered significant.

Results
O f 1207 rheumatoid arthritis patients whom we screened for enrollment, we excluded 297 because of chronic glucocorticoid use before admission and another 61 because they were lost to follow-up (Figure 1).In the end, we analyzed 849 patients, of whom 598 (70.4%) received perioperative glucocorticoids and 251 (29.6%) did not.The two groups did not exhibit statistically significant differences in terms of sex, age, body mass index, Charlson comorbidity index, or prevalence of diabetes (Table 1).In addition, there were no statistically significant differences in intraoperative conditions including intraoperative blood loss and blood transfusion between the two groups.Among those who received perioperative glucocorticoids, most received dexamethasone (73.6%), followed by methylprednisolone (16.2%) and hydrocortisone (10.2%).Patients who received perioperative glucocorticoids showed a similar incidence of acute complications within 90 days after surgery as those who did not receive glucocorticoids (2.3 vs. 4.0%, p = 0.187), and the incidence of specific complications did not differ significantly between the two groups (Table 2).The incidence of overall acute postoperative infection (2.0% vs. 2.8%, p = 0.482), periprosthetic joint infection (0.8% vs. 0.8%, p = 1.000), and superficial infection (1.2% vs. 2.0%, p = 0.335) were similar between the two groups.The two groups were also similar to each other in rates of mortality within 30 days and of readmission within 90 days.
A significantly larger proportion of patients who did not receive perioperative glucocorticoids required rescue opioids (44.6 vs. 17.9%,p < 0.001), and per-patient opioid consumption was significantly higher among those who did not receive glucocorticoids (8.9 AE 4.6 vs. 4.7 AE 2.1 mg, p < 0.001; Table 3).The two groups did not differ significantly in incidence of postoperative hyperglycemia or hypotension during hospitalization.

Discussion
O ur retrospective analysis of a reasonably large popula- tion of patients with rheumatoid arthritis undergoing  total joint arthroplasty suggests perioperative glucocorticoids use in these individuals did not increase incidence of acute complications, hypotension, and hyperglycemia after surgery, but reduce the postoperative need for rescue opioids.

Postoperative Complications
4][15][16] Our study further contributed valuable evidence to support the perioperative use of glucocorticoids in patients with rheumatoid arthritis.However, our results differ from a single study that associated higher perioperative glucocorticoid dosage with an increased risk of postoperative complications. 11We compared the differences in the cohorts included in our study and this study, and it is worth noting that this particular study included patients who were already receiving chronic glucocorticoid treatment prior to surgery, which may have contributed to the observed heightened risk. 10

Consumption of Opioids
The administration of perioperative glucocorticoids in patients with rheumatoid arthritis resulted in a decreased requirement for rescue opioids.Several studies have reported that in patients without rheumatoid arthritis, perioperative glucocorticoids can reduce the need for opioid rescue 17 as well as dampen pain and inflammation. 18However, none of these studies included patients with rheumatoid arthritis.Given the potentially heightened inflammatory activity in patients with rheumatoid arthritis, our study contributes to the existing evidence supporting glucocorticoid treatment to relieve postoperative pain and reduce opioid consumption.

Hyperglycemia and Hypotension
Perioperative glucocorticoids did not significantly increase the incidence of hyperglycemia in our patients following total joint arthroplasty.This finding contradicts previous studies that have linked glucocorticoid use to hyperglycemia after total joint arthroplasty in diabetic patients, 19,20 but not in patients with well-controlled glycemic levels. 21Considering the presence of abnormal glucose metabolism in diabetic patients, the administration of corticosteroids at doses exceeding physiological levels may disrupt the delicate balance and result in an increased incidence of hyperglycemia.However, this issue may be ameliorated in non-diabetic patients.Similarly, perioperative glucocorticoids did not significantly affect incidence of hypotension in our patients after total joint arthroplasty.While physiological doses of perioperative glucocorticoids appear not to alter risk of adrenal insufficiency after orthopaedic surgery, 22 higher doses have been recommended as a way to prevent hypotension. 23uture studies should continue to explore the effects of perioperative glucocorticoids on blood pressure and blood glucose.

Strengths and Limitations
Indeed, all our findings should be verified and extended in larger, preferably multi-center studies that prospectively examine the influence of type, dose, and frequency of perioperative glucocorticoids with sufficiently long follow-up to reliably detect differences in complications, including those that occur later, such as periprosthetic joint infection.In this way, the present work justifies closer consideration of perioperative glucocorticoids to alleviate pain in individuals with rheumatoid arthritis.

Conclusion
P erioperative glucocorticoids may reduce the need for res- cue opioids after total joint arthroplasty of rheumatoid arthritis patients, without increasing the incidence of acute complications, hypotension, or hyperglycemia.

Acknowledgments
T he authors would like to thank those researchers who made valuable contributions to this endeavor.

Conflict of Interest Statement
T he authors have no relevant financial or non-financial interests to disclose.

Figure 1
Figure 1 Flow diagram of patient selection and analysis.RA, rheumatoid arthritis; TJA, total joint arthroplasty.

Table 1
Clinicodemographic characteristics of patients, stratified by perioperative glucocorticoid use.

Table 2
Comparison of acute complications within 90 days after total joint arthroplasty between patients who received perioperative glucocorticoids or not.
Note: Values are n or n (%), unless otherwise noted.;Abbreviation: ND, not done.

Table 3
Comparison of opioid consumption, hyperglycemia and hypotension after total joint arthroplasty between patients who received perioperative glucocorticoids or not.Values are n (%) or mean AE SD, unless otherwise noted.; * Morphine equivalents.